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Normand Thierry


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tél : 02.38.25.55.36 - fax : 02.38.25.78.07

Publications

2013   Références trouvées : 1

Mollet L., Robinet P., Dubois M., Aurouet A., Normand T., Charpentier S., Sureau A., Grandclement C., Garnache-Ottou F., Deconinck E., Brulé F., Rohrlich P.S. and Legrand A.  (2013)

Opposing Mcl-1, the GALIG proapoptotic gene is upregulated as neutrophils die and underexpressed in Acute Myeloid Leukemia cells

Molecular Immunology 56 (1-2) 123-128
GALIG gene expression induces apoptosis in cultured cells through a pathway still under investigation. It is highly expressed in leukocytes but weakly detectable in bone marrow, suggesting a role in the myeloid lineage homeostasis. We show here that GALIG-induced cell death is counteracted by the overexpression of MCL-1, a pro-survival member of the Bcl2 family. Moreover, during spontaneous neutrophil apoptosis, a substantial increase in GALIG gene expression is observed : GALIG still opposes MCL-1. Finally, in bone marrow and peripheral blood cells from patients with Acute Myeloid Leukemia type 2, the level of GALIG transcripts is massively down-regulated when compared to their normal counterparts, while MCL-1 is expressed to the same extent. These data suggest that GALIG could be a key player in the cell death pathway involved in leukocytes homeostasis and myeloid malignancies.

GALIG gene expression induces apoptosis in cultured cells through a pathway still under investigation. It is highly expressed in leukocytes but weakly detectable in bone marrow, suggesting a role in the myeloid lineage homeostasis. We show here that GALIG-induced cell death is counteracted by the overexpression of MCL-1, a pro-survival member of the Bcl2 family. Moreover, during spontaneous neutrophil apoptosis, a substantial increase in GALIG gene expression is observed : GALIG still opposes MCL-1. Finally, in bone marrow and peripheral blood cells from patients with Acute Myeloid Leukemia type 2, the level of GALIG transcripts is massively down-regulated when compared to their normal counterparts, while MCL-1 is expressed to the same extent. These data suggest that GALIG could be a key player in the cell death pathway involved in leukocytes homeostasis and myeloid malignancies.


2010   Références trouvées : 1

Robinet, P., Mollet, L., Gonzalez, P., Normand, T., Charpentier, S., Brule, F., Dubois, M. & Legrand, A.  (2010)

The mitogaligin protein is addressed to the nucleus via a non-classical localization signal.

Biochem. Biophys. Res. Commun. 392, 53-57.


2009   Références trouvées : 2

Sennepin, A.D., Charpentier, S., Normand, T., Sarre, C., Legrand, A. & Mollet, L.M.  (2009)

Multiple reprobing of Western blots after inactivation of peroxidase activity by its substrate, hydrogen peroxide.

Anal. Biochem. 393, 129-131.

Gonzalez, P., Robinet, P., Charpentier, S., Mollet, L., Normand, T., Dubois, M. & Legrand, A.  (2009)

Apoptotic activity of a nuclear form of mitogaligin, a cell death protein.

Biochem. Biophys. Res. Commun. 378, 816-820.


2007   Références trouvées : 1

Gonzalez, P ; Duneau, M ; Charpentier, S ; Normand, T ; Mollet, L ; Dubois, M ; Legrand, A  (2007)

Destabilization of membranes containing cardiolipin or its precursors by peptides derived from mitogaligin, a cell death protein

Biochemistry 46 (25) 7374-7382
Galig, a gene embedded within the galectin-3 gene, induces cell death when transfected in human cells. This death is associated with cell shrinkage, nuclei condensation, and aggregation of mitochondria. Galig contains two different overlapping open reading frames encoding two unrelated proteins. Previous observations have shown that one of these proteins, named mitogaligin, binds to mitochondria and promotes the release of cytochrome c. However, the mechanism of action of this cytotoxic protein remains still obscure.

Galig, a gene embedded within the galectin-3 gene, induces cell death when transfected in human cells. This death is associated with cell shrinkage, nuclei condensation, and aggregation of mitochondria. Galig contains two different overlapping open reading frames encoding two unrelated proteins. Previous observations have shown that one of these proteins, named mitogaligin, binds to mitochondria and promotes the release of cytochrome c. However, the mechanism of action of this cytotoxic protein remains still obscure.


2005   Références trouvées : 1

Duneau, M ; Boyer-Guittaut, M ; Gonzalez, P ; Charpentier, S ; Normand, T ; Dubois, M ; Raimond, J ; Legrand, A  (2005)

Galig, a novel cell death gene that encodes a mitochondrial protein promoting cytochrome c release

Experimental Cell Research 302 (2) 194-205
Galectin-3 internal gene (Galig) was recently identified as an internal gene transcribed from the second intron of the human galectin-3 gene that is implicated in cell growth, cell differentiation, and cancer development. In this study, we show that galig expression causes morphological alterations in human cells, such as cell shrinkage, cytoplasm vacuolization, nuclei condensation, and ultimately cell death. These alterations were associated with extramitochondrial release of cytochrome c, a known cell death effector.

Galectin-3 internal gene (Galig) was recently identified as an internal gene transcribed from the second intron of the human galectin-3 gene that is implicated in cell growth, cell differentiation, and cancer development. In this study, we show that galig expression causes morphological alterations in human cells, such as cell shrinkage, cytoplasm vacuolization, nuclei condensation, and ultimately cell death. These alterations were associated with extramitochondrial release of cytochrome c, a known cell death effector.


2001   Références trouvées : 1

Guittaut, M ; Charpentier, S ; Normand, T ; Dubois, M ; Raimond, J ; Legrand, A  (2001)

Identification of an internal gene to the human galectin-3 gene with two different overlapping reading frames that do not encode galectin-3

Journal of Biological Chemistry 276 (4) 2652-2657
We previously reported that alternative transcripts were initiated within the second intron of the human Galectin-3 gene (LGALS3), We now demonstrate that these transcripts arise from an internal gene embedded within LGALS3 and named galig (Galectin-3 internal gene). Tissue-specific expression of galig was assayed by screening of several human tissues. Contrary to LGALS3, galig appears to be tightly regulated and principally activated in leukocytes from peripheral blood. Cloning and characterization of galig transcripts revealed that they contain two out-of-frame overlapping open-reading frames (ORFs). Transfection of expression vectors encoding enhanced green fluorescent protein (EGFP) chimeras indicated that both ORFs could be translated in proteins unrelated to Galectin-3. The ORF1 polypeptide targets EGFP to cytosol and nucleus whereas ORF2 targets EGFP to mitochondria. These results revealed the exceptional genetic organization of the LGALS3 locus.

We previously reported that alternative transcripts were initiated within the second intron of the human Galectin-3 gene (LGALS3), We now demonstrate that these transcripts arise from an internal gene embedded within LGALS3 and named galig (Galectin-3 internal gene). Tissue-specific expression of galig was assayed by screening of several human tissues. Contrary to LGALS3, galig appears to be tightly regulated and principally activated in leukocytes from peripheral blood. Cloning and characterization of galig transcripts revealed that they contain two out-of-frame overlapping open-reading frames (ORFs). Transfection of expression vectors encoding enhanced green fluorescent protein (EGFP) chimeras indicated that both ORFs could be translated in proteins unrelated to Galectin-3. The ORF1 polypeptide targets EGFP to cytosol and nucleus whereas ORF2 targets EGFP to mitochondria. These results revealed the exceptional genetic organization of the LGALS3 locus.


1996   Références trouvées : 1

Morissette, J ; Durocher, F ; Leblanc, JF ; Normand, T ; Labrie, F ; Simard, J  (1996)

Genetic linkage mapping of the human steroid 5 alpha-reductase type 2 gene (SRD5A2) close to D2S352 on chromosome region 2p23->p22

Cytogenetics and Cell Genetics 73 (4) 304-307
Two steroid 5 alpha-reductase isoenzymes catalyze the conversion of testosterone into dihydrotestosterone, the more bioactive androgen, which is essential for male phenotypic sexual differentiation and for androgen-mediated growth of such tissues and organs as the prostate. Inherited mutations in SRD5A2 cause male pseudohermaphroditism. The SRD5A1 and SRD5A2 genes encoding the steroid 5 alpha-reductase type 1 and type 2 isoenzymes have been previously assigned by in situ hybridization to 5p15 and 2p23, respectively.

Two steroid 5 alpha-reductase isoenzymes catalyze the conversion of testosterone into dihydrotestosterone, the more bioactive androgen, which is essential for male phenotypic sexual differentiation and for androgen-mediated growth of such tissues and organs as the prostate. Inherited mutations in SRD5A2 cause male pseudohermaphroditism. The SRD5A1 and SRD5A2 genes encoding the steroid 5 alpha-reductase type 1 and type 2 isoenzymes have been previously assigned by in situ hybridization to 5p15 and 2p23, respectively.


1995   Références trouvées : 3

Adamski, J ; Normand, T ; Leenders, F ; Monte, D ; Begue, A ; Stehelin, D ; Jungblut, PW ; Delaunoit, Y  (1995)

Molecular-cloning of a novel widely expressed human 80 KDA 17-ß-hydroxysteroid dehydrogenase-IV

Biochemical Journal 311 437-443 Part 2
Reactions of oestrogens and androgens at position C-17 are catalysed by 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs). Cloning of the cDNA of a novel human 17 beta-HSD IV and expression of its mRNA are described. A probe derived from the recently discovered porcine 17 beta-oestradiol dehydrogenase (17 beta-EDH) was used to isolate a 2.6 kb human cDNA encoding a continuous protein of 736 amino acids of high (84 %) similarity to the porcine 17 beta-EDH. The calculated molecular mass of the human enzyme is 79 595 Da. Other sequence similarities shared by the two enzymes are : an N-terminal sequence which is similar to that of members of the short-chain alcohol dehydrogenase family ; amino acids 343-607 which are similar to the C-terminal domains of a trifunctional Candida tropicalis enzyme and the FOX2 gene product of Saccharomyces cerevisiae ; amino acids 596-736 which are similar to human sterol carrier protein 2. The previously cloned human 17 beta-HSD I, II and III are less than 25% identical with 17 beta-HSD IV. mRNA for HSD IV is a single species of 3.0 kb, present in many tissues with highest concentrations in liver, heart, prostate and testes. When overexpressed in mammalian cells, the human 17 beta-HSD IV enzyme displays a specific unidirectional oxidative 17 beta-HSD activity.

Reactions of oestrogens and androgens at position C-17 are catalysed by 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs). Cloning of the cDNA of a novel human 17 beta-HSD IV and expression of its mRNA are described. A probe derived from the recently discovered porcine 17 beta-oestradiol dehydrogenase (17 beta-EDH) was used to isolate a 2.6 kb human cDNA encoding a continuous protein of 736 amino acids of high (84 %) similarity to the porcine 17 beta-EDH. The calculated molecular mass of the human enzyme is 79 595 Da. Other sequence similarities shared by the two enzymes are : an N-terminal sequence which is similar to that of members of the short-chain alcohol dehydrogenase family ; amino acids 343-607 which are similar to the C-terminal domains of a trifunctional Candida tropicalis enzyme and the FOX2 gene product of Saccharomyces cerevisiae ; amino acids 596-736 which are similar to human sterol carrier protein 2. The previously cloned human 17 beta-HSD I, II and III are less than 25% identical with 17 beta-HSD IV. mRNA for HSD IV is a single species of 3.0 kb, present in many tissues with highest concentrations in liver, heart, prostate and testes. When overexpressed in mammalian cells, the human 17 beta-HSD IV enzyme displays a specific unidirectional oxidative 17 beta-HSD activity.

Normand, T ; Husen, B ; Leenders, F ; Pelczar, H ; Baert, JL ; Begue, A ; Flourens, AC ; Adamski, J ; deLaunoit, Y  (1995)

Molecular characterization of mouse 17 beta-hydroxysteroid dehydrogenase IV

Journal of Steroid Biochemistry and Molecular Biology 55 (5-6) 541-548
17 beta-hydroxysteroid dehydrogenases (17 beta-HSD) catalyze the conversion of estrogens and androgens at the C17 position. The 17 beta-HSD type I, II, III and IV share less than 25% amino acid similarity. The human and porcine 17 beta-HSD N reveal a three-domain structure unknown among other dehydrogenases. The N-terminal domains resemble the short chain alcohol dehydrogenase family while the central parts are related to the C-terminal parts of enzymes involved in peroxisomal beta-oxidation of fatty acids and the C-terminal domains are similar to sterol carrier protein 2. We describe the cloning of the mouse 17 beta-HSD IV cDNA and the expression of its mRNA.

17 beta-hydroxysteroid dehydrogenases (17 beta-HSD) catalyze the conversion of estrogens and androgens at the C17 position. The 17 beta-HSD type I, II, III and IV share less than 25% amino acid similarity. The human and porcine 17 beta-HSD N reveal a three-domain structure unknown among other dehydrogenases. The N-terminal domains resemble the short chain alcohol dehydrogenase family while the central parts are related to the C-terminal parts of enzymes involved in peroxisomal beta-oxidation of fatty acids and the C-terminal domains are similar to sterol carrier protein 2. We describe the cloning of the mouse 17 beta-HSD IV cDNA and the expression of its mRNA.

Simon, AM ; Guilbaud, C ; Normand, T ; Jean-Faucher, CH ; Veyssière, G ; Jean CL  (1995)

Developmental and hormonal regulation of specific proteins in mouse seminal vesicles. Isolation and characterization of genomic and cDNA clones for an androgen-regulated secretory protein.

Experimental and Clinical Endocrinology (Life Sci. Adv.) 14 73-82


1993   Références trouvées : 2

Simard, J ; Feunteun, J ; Lenoir, G ; Tonin, P ; Normand, T ; The, VL ; Vivier, A ; Lasko, D ; MORGAN, K ; Rouleau, GA ; Lynch, H ; Labrie, F ; Narod, SA  (1993)

Genetic-mapping of the breast-ovarian cancer syndrome to a small interval on chromosome-17q12-21 - exclusion of candidate genes edh17b2 and rara

Human Molecular Genetics 2 (8) 1193-1199
A susceptibility gene for hereditary breast-ovarian cancer, BRCA1, has been assigned by linkage analysis to chromosome 17q21. Candidate genes in this region include EDH17B2, which encodes estradiol 17beta-hydroxysteroid dehydrogenase II (17beta-HSD II), and RARA, the gene for retinoic acid receptor alpha. We have typed 22 breast and breast-ovarian cancer families with eight polymorphisms from the chromosome 17q12-21 region, including two in the EDH17B2 gene. Genetic recombination with the breast cancer trait excludes RARA from further consideration as a candidate gene for BRCA1. Both BRCA1 and EDH17B2 map to a 6 cM interval (between THRA1 and D17S579) and no recombination was observed between the two genes.

A susceptibility gene for hereditary breast-ovarian cancer, BRCA1, has been assigned by linkage analysis to chromosome 17q21. Candidate genes in this region include EDH17B2, which encodes estradiol 17beta-hydroxysteroid dehydrogenase II (17beta-HSD II), and RARA, the gene for retinoic acid receptor alpha. We have typed 22 breast and breast-ovarian cancer families with eight polymorphisms from the chromosome 17q12-21 region, including two in the EDH17B2 gene. Genetic recombination with the breast cancer trait excludes RARA from further consideration as a candidate gene for BRCA1. Both BRCA1 and EDH17B2 map to a 6 cM interval (between THRA1 and D17S579) and no recombination was observed between the two genes.

Normand, T ; Narod, S ; Labrie, F ; Simard, J  (1993)

Detection of polymorphisms in the estradiol 17-beta-hydroxysteroid dehydrogenase-ii gene at the edh17b2 locus on 17q11-q21

Human Molecular Genetics 2 (4) 479-483
The human estradiol 17beta-hydroxysteroid dehydrogenase II (17beta-HSD II) gene has been assigned by somatic cell hybridization to chromosome 17q11 - q21, near the region of assignment of the gene BRCA1, which is involved in hereditary breast-ovarian cancer. The nucleotide sequence of 17beta-HSD II was completely determined in four unrelated individuals. Direct sequencing of PCR fragments that span the complete 17beta-HSD II gene revealed a total of 11 allelic variants which were due to single base substitutions. The presence of these variants was then studied in twenty six additional unrelated individuals. There were nine frequent and two rare polymophisms. Seven of the 11 polymorphisms were in complete linkage disequilibrium. These polymorphisms in the 17beta-HSD II gene provide markers that can be used for the genetic mapping of this locus, and may be used to establish whether 17beta-HSD II is a candidate gene for hereditary breast-ovarian cancer.

The human estradiol 17beta-hydroxysteroid dehydrogenase II (17beta-HSD II) gene has been assigned by somatic cell hybridization to chromosome 17q11 - q21, near the region of assignment of the gene BRCA1, which is involved in hereditary breast-ovarian cancer. The nucleotide sequence of 17beta-HSD II was completely determined in four unrelated individuals. Direct sequencing of PCR fragments that span the complete 17beta-HSD II gene revealed a total of 11 allelic variants which were due to single base substitutions. The presence of these variants was then studied in twenty six additional unrelated individuals. There were nine frequent and two rare polymophisms. Seven of the 11 polymorphisms were in complete linkage disequilibrium. These polymorphisms in the 17beta-HSD II gene provide markers that can be used for the genetic mapping of this locus, and may be used to establish whether 17beta-HSD II is a candidate gene for hereditary breast-ovarian cancer.


1992   Références trouvées : 3

Bergeron, J ; Normand, T ; Bharucha, A ; Venmurthy, MR ; Julien, P ; Gagne, C ; Dionne, C ; Debraekeleer, M ; Brun, D ; Hayden, MR ; Lupien, PJ  (1992)

Prevalence, geographical-distribution and genealogical investigations of mutation-188 of lipoprotein-lipase gene in the french-canadian population of quebec

Clinical Genetics 41 (4) 206-210
Familial lipoprotein lipase deficiency (FLD) is of particular interest to the French Canadian population of Quebec since the largest concentration of homozygotes and carriers of this genetic disease in the world resides in this area. We have previously described a missense mutation (M-188) in the lipoprotein lipase (LPL) gene which was present in FLD patients belonging to different ancestries, including a number of French Canadians (Monsalve MV et al. J Clin Invest 1990 : 86 : 728-734). In the present report, we show that this mutation, although found in largest absolute numbers among French Canadians as compared to other groups in the world, accounts for only a small proportion (24%) of all the LPL mutant alleles in this population. The M-188 occurs either in the homozygote state or as a compound heterozygote with another LPL mutation. Analysis of geographic distribution indicates that the M-188 is more prevalent in western Quebec, with the highest carrier rate in the Mauricie region. Genealogical reconstruction leads to the recognition of four founders for M-188, all emigrants from France to Quebec in the 17th century.

Familial lipoprotein lipase deficiency (FLD) is of particular interest to the French Canadian population of Quebec since the largest concentration of homozygotes and carriers of this genetic disease in the world resides in this area. We have previously described a missense mutation (M-188) in the lipoprotein lipase (LPL) gene which was present in FLD patients belonging to different ancestries, including a number of French Canadians (Monsalve MV et al. J Clin Invest 1990 : 86 : 728-734). In the present report, we show that this mutation, although found in largest absolute numbers among French Canadians as compared to other groups in the world, accounts for only a small proportion (24%) of all the LPL mutant alleles in this population. The M-188 occurs either in the homozygote state or as a compound heterozygote with another LPL mutation. Analysis of geographic distribution indicates that the M-188 is more prevalent in western Quebec, with the highest carrier rate in the Mauricie region. Genealogical reconstruction leads to the recognition of four founders for M-188, all emigrants from France to Quebec in the 17th century.

Normand, T ; Bergeron, J ; Fernandezmargallo, T ; Bharucha, A ; Venmurthy, MR ; Julien, P ; Gagne, C ; Dionne, C ; Debraekeleer, M ; MA, R ; Hayden, MR ; Lupien, PJ  (1992)

Geographic-distribution and genealogy of mutation 207 of the lipoprotein-lipase gene in the french-canadian population of quebec

Human Genetics 89 (6) 671-675
Mutations in the lipoprotein lipase (LPL) gene, leading to partial or total inactivation of the enzyme, result in a hereditary clinical syndrome called familial LPL deficiency. The French Canadian population, which is primarily and historically located in the province of Quebec, has the highest worldwide frequency of LPL-deficient patients. We have analyzed the prevalence, spatial distribution, and genealogy in the Quebec population of a LPL gene mutation, M-207 (P207L in conventional notation), which changes the amino acid proline to leucine in position 207 of the LPL protein and inactivates the enzyme.

Mutations in the lipoprotein lipase (LPL) gene, leading to partial or total inactivation of the enzyme, result in a hereditary clinical syndrome called familial LPL deficiency. The French Canadian population, which is primarily and historically located in the province of Quebec, has the highest worldwide frequency of LPL-deficient patients. We have analyzed the prevalence, spatial distribution, and genealogy in the Quebec population of a LPL gene mutation, M-207 (P207L in conventional notation), which changes the amino acid proline to leucine in position 207 of the LPL protein and inactivates the enzyme.

Peeva, E ; Brun, LD ; Murthy, MRV ; Despres, JP ; Normand, T ; Gagne, C ; Lupien, PJ ; Julien, P  (1992)

Adipose cell-size and distribution in familial lipoprotein-lipase deficiency

International Journal of Obesity 16 (10) 737-744
To determine the effect of lipoprotein lipase deficiency on the size distribution of fat cell populations in human adipose tissues, abdominal and femoral subcutaneous fat tissue biopsies were obtained from seven patients affected by familial hyperchylomicronaemia. These patients were characterized by massive accumulation of chylomicrons in the fasting state due to defective catabolism of plasma triglyceride-rich lipoproteins. They had no post-heparin plasma lipoprotein lipase activity and their fat tissues were deficient in lipoprotein lipase activity.

To determine the effect of lipoprotein lipase deficiency on the size distribution of fat cell populations in human adipose tissues, abdominal and femoral subcutaneous fat tissue biopsies were obtained from seven patients affected by familial hyperchylomicronaemia. These patients were characterized by massive accumulation of chylomicrons in the fasting state due to defective catabolism of plasma triglyceride-rich lipoproteins. They had no post-heparin plasma lipoprotein lipase activity and their fat tissues were deficient in lipoprotein lipase activity.


1991   Références trouvées : 1

Ma, YH ; Henderson, HE ; Venmurthy, MR ; Roederer, G ; Monsalve, MV ; Clarke, LA ; Normand, T ; Julien, P ; Gagne, C ; Lambert, M ; Davignon, J ; Lupien, PJ ; Brunzell, J ; Hayden, MR  (1991)

A mutation in the human lipoprotein-lipase gene as the most common cause of familial chylomicronemia in french-canadians

New England Journal of Medicine 324 (25) 1761-1766
Background. Lipoprotein lipase hydrolyzes the triglyceride core of chylomicrons and very-low-density lipoproteins and has a crucial role in regulating plasma lipoprotein levels. Deficiencies of lipoprotein lipase activity lead to aberrations in lipoprotein levels. Worldwide, the frequency of lipoprotein lipase deficiency is highest among French Canadians. We sought to determine the molecular basis of the disorder in this population. Methods. The entire coding sequence of the lipoprotein lipase gene from one French Canadian patient was amplified by the polymerase chain reaction and sequenced. Exon 5 from 36 other French Canadian patients was amplified and analyzed by dot blot hybridization with allele-specific oligonucleotides. Results.

Background. Lipoprotein lipase hydrolyzes the triglyceride core of chylomicrons and very-low-density lipoproteins and has a crucial role in regulating plasma lipoprotein levels. Deficiencies of lipoprotein lipase activity lead to aberrations in lipoprotein levels. Worldwide, the frequency of lipoprotein lipase deficiency is highest among French Canadians. We sought to determine the molecular basis of the disorder in this population. Methods. The entire coding sequence of the lipoprotein lipase gene from one French Canadian patient was amplified by the polymerase chain reaction and sequenced. Exon 5 from 36 other French Canadian patients was amplified and analyzed by dot blot hybridization with allele-specific oligonucleotides. Results.


1990   Références trouvées : 1

Normand, T ; Jeanfaucher, C ; Jean, C  (1990)

Neonatal exposure to estrogens alters the protein profiles and gene-expression in the genital-tract of adult male-mice

Journal of Steroid Biochemistry and Molecular Biology 36 (5) 415-423


1989   Références trouvées : 1

Normand, T ; Jeanfaucher, C ; Jean, C  (1989)

Developmental pattern of androgen-regulated proteins in seminal-vesicles from the mouse

International Journal of Andrology 12 (3) 219-230


Mots-clés

Maître de conférences , Mort cellulaire programmée